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Abstract
Primary central nervous system lymphoma (PCNSL) is an aggressive and rare disease. Autophagy is a catabolic mechanism boosting various tumors, including lymphomas; its inhibition is thus a promising therapeutic target. Its presence has never been studied in PCNSLs. We conducted a retrospective immunohistochemical study of 25 PCNSLs for LC3B, p62, and M6PR, comparing it with clinicopathological characteristics. Fourteen (56%) and eleven (44%) PCNSLs were of low and high LC3B expression, respectively. p62 expression was present in most tumors (n = 21, 84%). M6PR was present in all tumors, with 14 (56%) and 11 (44%) cases being of low and high M6PR expression, respectively. LC3B expression was correlated with the performance status (PS) (p = 0.04). No association was found with other clinical parameters, such as deep structure invasion, multiple lesions, complete response, and recurrence after response. p62 showed a strong positive association with MUM1 expression (p = 0.0005). M6PR expression showed a positive correlation (p = 0.04) with PD-L1 expression. No association was found with p53, Ki67, CD8, BCL2, BCL6, or double MYC/BLC2 co-expressors. No association of LC3B, p62, and M6PR expression with survival was found. Our findings provide evidence for the possible presence of autophagic markers in PCNSLs and, thus, for possible treatment targets.
Highlights
Primary central nervous system lymphoma (PCNSL) is an aggressive and rare disease
Baseline immunohistochemical features with prognostic features according to previous studies were recorded: The immunohistochemical classification scheme developed by Hans et al for systemic diffuse large B-cell lymphoma (DLBCL) subdividing tumors into germinal center B-cell-like (GCB) and non-germinal-center-like (ABC-activated B cell) based on the expression patterns for CD10, BCL6, and MUM1 was u sed[9]
Previous studies in systemic lymphomas have shown that higher expression of Beclin 1, a protein implicated in autophagy regulation, is associated with better prognosis in various forms of non-Hodgkin lymphomas[18], including extranodal natural killer T-cell lymphoma[19] and D LBCL20; the exact mechanism underlying this observation is unknown
Summary
Primary central nervous system lymphoma (PCNSL) is an aggressive and rare disease. Autophagy is a catabolic mechanism boosting various tumors, including lymphomas; its inhibition is a promising therapeutic target. Primary diffuse large B-cell lymphoma (DLBCL) of the central nervous system (CNS) is an aggressive and rare lymphoma of the brain, spinal cord, leptomeninges, or eye[1]. It accounts for < 1% of all non-Hodgkin lymphomas and around 3% of all brain tumors, with an overall annual incidence rate of 0.47/100,000 p opulation[1]. The cation-independent mannose-6-phosphate receptor (M6PR) is the prototypical lysosome-targeting receptor and the main endosomal marker associated with the autophagic m achinery[6]. The aim of this study was to investigate the possible presence of autophagic markers in PCNSLs and to compare it with the clinicopathological prognostic features of this disease
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